Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase.
Level 2 - randomized trial
Individual randomized crossover trial and within-subject experimental challenge
PubMed 37735274 · doi:10.1038/s42255-023-00869-w
What was done
Eleven women underwent four hyperinsulinemic-euglycemic clamps (two in the follicular phase and two in the luteal phase) in a fourfold crossover design comparing intranasal insulin spray to placebo spray, with change in glucose infusion rate as the primary endpoint. In a separate cohort of 15 women, hypothalamic insulin responsiveness was measured using functional magnetic resonance imaging (fMRI) following intranasal insulin administration across both menstrual cycle phases in a within-subject design.
What was found
During the follicular phase, intranasal insulin administration significantly increased the required glucose infusion rate compared to placebo, remaining statistically significant after adjusting for blood glucose and insulin concentrations. In contrast, during the luteal phase, no significant effect of intranasal insulin on glucose infusion rate was detected after adjustment. In the imaging cohort, hypothalamic responsiveness was altered by insulin in the follicular phase but not in the luteal phase. The abstract did not report exact numerical values, effect sizes, or p-values.
Why it matters
These findings indicate that central insulin regulation of whole-body insulin sensitivity in women is dependent on the menstrual cycle phase. This mechanism may explain cycle-dependent fluctuations in metabolic regulation and luteal-phase insulin resistance.
Limits
The study had very small sample sizes (n=11 for metabolic clamps and n=15 for fMRI). The abstract lacks quantitative data, confidence intervals, and exact p-values. Clinical metabolic endpoints and long-term implications for conditions such as diabetes or PCOS were not evaluated.
Cited by
- supports A transient state of insulin resistance occurs in the week prior to menstruation (the late luteal phase).